Microscale methods have previously been used for finding new combinations of ligands and binders for screening libraries of compounds for
(a) new drug candidates which are based on a receptor-ligand interaction, and
(b) new ligand candidates for affinity assays, affinity chromatography etc. Microscale methods have also been suggested for optimizing the conditions for formation or dissociation of a particular affinity complex or when selecting affinity counterparts for other reasons.
Microscale methods have also been used for determining the amount of a particular compound (analyte) in a sample.
Methods have been used that are based on affinity capture of a binder or an analyte by an affinity counterpart that is immobilized or immobilizable to a solid phase.
Typically the formation of the complex on a solid phase has been performed under non-flow-conditions. See for instance Eteshola et al, Sensors and Actuators B 72 (2001) 129-133; Sato et al, Anal. Chem. 72 (2000) 1144-1147; and WO 9721090 (camera, Mian et al).
Non-flow conditions will simplify the methods but information that only can be obtained from experiments performed under flow conditions will be missed. For small molecules non-flow conditions may be acceptable because their diffusion rates are often relatively high and orientation of their binding sites for binding is uncomplicated. This is normally not applicable to larger molecules. Without controlling the liquid flow accurate information will be difficult to obtain for large molecules.
Recently a MALDI MS integrated microfluidic affinity system based on affinity binding to a reverse phase matrix has been presented. In this system a protein digest was adsorbed to a reverse phase matrix and subsequently desorbed and transported to an outlet port that functioned as a MALDI MS target. (Integrated sample preparation and MALDI MS on a microfluidic compact disc (CD with improved sensitivity) (Magnus Gustavsson et al) ASMS 2001. The demand on the reproducibility in the binding, the control of the liquid flow rate, and the residence time was low.
WO 0138865 (Univ. of Alberta, Harrison et al) describes a solid phase extraction method in a singular microchannel structure utilizing flow conditions and affinity binding. In another example the publication shows saturation of solid phase bound anti-theopyhilline antibodies with theophylline.